Cardiac and vascular toxicity of amivantamab in non-small cell lung cancer (NSCLC): A systematic review

Amivantamab, a newly introduced drug for locally advanced or metastatic NSCLC in patients with EXON-20 mutation, has shown promising results for prolonging progression-free survival and overall survival. Amivantamab’s toxicities are common, especially those related to skin and infusion. However, its cardiovascular related toxicities are less examined. Therefore, the aim of this study was to perform a systematic review and concentrate available data for the cardiovascular toxicities of amivantamab in patients with NSCLC. This review was performed according to the PRISMA guidelines, and relevant studies were searched on three scientific databases, PubMed, Cochrane Library and ScienceDirect. In total, four phase-3 randomized clinical trials, three phase-1 clinical trials, and two real-world study were included in this systematic review. The results revealed that grade ≥ 3 cardiovascular toxicities are low in amivantamab monotherapy (<10 %), but their frequency increases when combined with lazertinib and overcome 20 % when amivantamab is combined with both lazertinib and chemotherapy. In addition, up to 3 % grade 5 cardiovascular events have been reported when amivantamab is combined with lazertinib. Pulmonary embolism and venous thromboembolism are the most common cardiovascular toxicities reported for amivantamab, and their risk increases when combined with lazertinib. These results indicate that amivantamab may be cardiotoxic, especially when combined with lazertininb, and cardioprotection should be considered in patients under amivantamab treatment.